The invention relates to a magnetic field applicator for heating magnetic substances in biological tissue for use in administering hyperthermia and thermo-ablation procedures, as well as having other medical and industrial applications.
Cancer diseases are treated in a generally known manner through surgical removal, chemotherapy, radiation therapy or a combination of these methods. Each of these methods is subject to certain limitations, especially at advanced stages following metastasis, when the tumor is located close to critical body areas. In cases of diffused tumor growth with uncertain localization, surgical removal of the tumor is either not possible or offers only minimal chances for a cure. For this reason, surgical intervention is generally combined with radiation therapy and chemotherapy. Radiation therapy is only as precise as the localization of the tumor by means of an image-producing processes, with the utmost care taken to avoid the destruction of healthy tissue. Chemotherapeutic means on the other hand, act systemically over the entire body. With this method, bone marrow toxicity or lack of specificity of the therapy limit the treatment ability. Undesirable side effects and damage to healthy tissue are often the unavoidable consequences with these therapy methods using the present state of the art. Improvement is therefore needed.
Over the last few years, hyperthermia has gained significance as an alternative procedure, which works by heating the tumor tissue to temperatures above 41xc2x0 C. This process provides an increased success in cancer treatment due to the increased local control, and in combination with surgery, radiation therapy and chemotherapy, improves the chance of survival. With temperatures between 41 and 46xc2x0 C., and with the natural assistance of the body, a controlled and rather slow reduction of the tumor tissue takes place. Acute destruction of cells starts to take place at higher temperatures starting at 47xc2x0 C. Depending on temperature, the form of necrosis, coagulation or carbonization, is either called hyperthermia (between 41 and 46xc2x0 C.) or thermo-ablation (above 47xc2x0 C.). Until the present invention, hyperthermia systems were considered to be suitable only for the above-mentioned hyperthermia or thermo-ablation procedures, having no other medial applications.
One general problem with hyperthermia systems according to the state of the art, is that no precisely localized and homogenous heating of a target region of a body is, as a general rule, possible. This was possible under certain physiological conditions (e.g. oxygen deprivation, low pH), when the tumor cells become sensitive to hyperthermia, but this only applies in a few isolated circumstances. Hyperthermia by itself is not any more effective on tumor cells than on normal tissue. For this reason, limiting the heating of tissue to the area indicated for treatment (which need not necessarily be confined to the tumor) is especially important, and not realized according to the state of the art. Thus, there is need for improvement.
According to the state of the art, systems dominated by electrical fields, radiate the electromagnetic waves in the megahertz range from antennae or other antenna-shaped objects or arrays of antennae, for regional hyperthermia. For so-called interstitial hyperthermia the electrical field of individual electrical-field applicators is used, and for deep hyperthermia the interference from an antenna array is used. It is a difficulty common to all of these electrical-field-dominated systems that the power consumption of target tissue can only be regulated by means of complex and expensive controls over the electrical field. Furthermore, the heating depends on the electrical conductivity of the applicable target tissue, which is by its very nature heterogeneous, so that an uneven heating of the electrical field is the likely result, even with homogenous radiation. Especially at the transition points of body regions, there is very different electrical conductivity. Excessive power can create xe2x80x9chot spotsxe2x80x9d that result in pain and burns inflicted on the patient. The consequence is a reduction of the total emitted power necessary for proper treatment of the patient, so that as a result the temperature required to irreversibly damage the tumor tissue (41-42xc2x0 C.) is not reached in the target region, and the therapy is not successful. Furthermore, due to the interference of dipole arrays, the production of a second electrical field maximum is only possible in areas further inside the body. For physical reasons, the greatest power consumption always takes place at the surface of the body, i.e. at the maximum radius. Added to this is the fact that the blood flow through the tumor and the surrounding normal tissue often changes under hyperthermia, and that this change cannot be compensated for by means of systems dominated by electrical fields from the outside because of the rather low control possibilities over the field.
Other processes according to the state of the art are ultrasound, preferably for thermo-ablation, and interstitial microwave applicators. The latter possess low penetration depth because of the frequency and can therefore only be used in the form of interstitial antennae. In addition, infrared for whole-body hyperthermia is used, as well as extra-corporeal systems to heat body fluids.
Furthermore, a hyperthermia process for the therapy of prostate cancer is disclosed in U.S. Pat. No. 5,197,940, hereinafter the ""940 patent, in which xe2x80x9cthermoseedsxe2x80x9d consisting of magnetic, in particular ferromagnetic or magnetizable material or containing such material, are implanted in the area of the tumor. These thermoseeds are typically several centimeters long, with a diameter in the millimeter range. It is necessary to implant such thermoseeds surgically, and at great cost. During treatment, the thermoseeds are subjected to an alternating magnetic field produced outside a patient""s body, whereby heat in the thermoseeds is produced by known hysteresis effects in form of hyperthermia.
These seeds are heated according to the xe2x80x9chot sourcexe2x80x9d principle that while the seeds are heated, the temperatures in the surroundings of the seed drop exponentially, so that the distance between the seeds may not be more than 1 cm in clinical application. In case of greater or uneven distances, thermal under-dosing occurs, which can prevent the success of the therapy. Especially with larger tumors, a very narrow implantation of the seed becomes necessary and the method becomes surgically expensive and stressful to the patient. Aside from the small distance, the seeds must be oriented parallel to the magnetic alternating field for optimal power consumption. The Curie temperature in so-called self-regulating thermoseeds prevents overheating by stopping further power consumption when the ferrite passes into a non-magnetizable state after the Curie temperature has been reached.
The ""940 patent discloses the use of a magnetic coil with an oscillatory circuit as the magnetic field applicator for the magnetic alternating field. A patient""s body region with the implanted thermoseeds can be placed in the axis of this oscillatory circuit. In practice, air coils are used in the central area where a patient is sitting on a non-magnetizable supporting plate during treatment.
In hyperthermia using thermoseeds, the high cost of surgery and the high intensity of the method, the risk of an imprecise orientation or a change in position of the seeds, the ensuing risk of thermal under-dosing, as well as a limitation of using this treatment method on tumors of smaller size are all disadvantages of this system.
In another known hyperthermia process disclosed in WO 97/43005 for tumor therapy, magnetizable microcapsules are proposed which reach the area of the tumor through the blood stream. In this way surgical implantation of magnetizable elements can be avoided, since with implantation, the danger exists that malignant tumor cells may be dispersed into healthy tissue when a cut is made into the tumor, in addition to the stress that a patient is subjected. A linear magnetic alternating field is used with a frequency in the range of 10 kHz to 500 kHz. The microcapsules are to be used in conjunction with a highly magnetizable material, so that the force of the magnetic alternating field, which is required for the field, can be managed with respect to the instrumentation structure of the required cooling system and the electrical energy supply. A practical instrumentation structure is however not indicated.
In a similar hyperthermia process disclosed in EP 0 913 167 A2, hereinafter EP167, rotating magnetic fields with a frequency greater than 10 kHz are used as fields. To produce the rotating magnetic alternating field, a magnetic field applicator is indicated only sketchily and schematically. The magnetic field applicator comprises a magnetic yoke with two pairs of pole shoes across from each other and separated each other by a gap in the exposure volume and two pairs of magnetic coils assigned to these pole shoes. More specifically, a rectangular magnetic yoke is shown whereby a pole shoe is aligned on the center of the rectangle, starting from the center of each yoke branch, so that a field space is formed. Cylinder coils are mounted on the pole shoes and face each other while being connected to an associated capacitor arrangement to form an oscillatory circuit.
The schematic representation of a magnetic field applicator disclosed in EP167 to carry out the above-mentioned hyperthermia process does not yet lead beyond the experimentation stage to a practical industrial solution, as is required for the sake of favorable production and operating costs, minimal space requirement and low field leakage, and optimal therapeutic effect for utilization under hospital conditions.
It is therefore an object of the present invention to create a magnetic field applicator for heating magnetic substances in biological tissue that produces a tightly focused magnetic field for transferring energy to a targeted tissue area selected for heating and at the same time to prevent unnecessarily heating health tissue.
It is therefore another object of the present invention to create a magnetic field applicator for heating magnetic substances in biological tissue that meet the requirements of cost, space, low field leakage, and effectively controlled heat distribution and conforms to industrial production standards for utilization under hospital conditions and other possible industrial applications.
It is therefore another object of the present invention to create a magnetic field applicator for heating magnetic substances in biological tissue that contains specifically oriented spacing gaps throughout the applicator for the removal of excess heat buildup and to produce a consistent and controlled energy flow for effective heating of the targeted tissue area during treatment.
The above objectives are accomplished according to the present invention by providing a magnetic field applicator for heating magnetic substances in biological tissue, having a magnetic yoke with two pole shoes across from each other separated by a prescribed space that defines magnetic field exposure volume, and with two magnetic coils, one assigned to each of the two pole shoes to produce a magnetic alternating field.
The magnetic yoke and poles shoes consist of groups of ferrite segments mounted together. Additionally, in the preferred embodiment, the magnetic field applicator is composed of a magnetic yoke having two parallel vertical yoke elements of identical geometry spaced apart a distance from each other and two transverse yoke elements disposed between said vertical yoke elements. The pole shoes, surrounded by magnetic disk-shaped coils, are attached to the center of said transverse yoke elements and oppose each other over a prescribed distance. In order to adjust the width of the space separating the pole shoes that defines the magnetic field exposure volume, one transverse yoke element with surrounding magnetic coil is designed to be an adjustable component relative to the other transverse yoke element. Advantageously, the closure of magnetic flux is subdivided on both sides into two paths of equal length and having the identical geometry. The mechanical aspects of adjusting one transverse yoke element relative to the other in this configuration is easily implemented and much simpler than in a design with only one vertical yoke element, since the two vertical yoke elements can be utilized as supports for either side.
Conducting a hyperthermia procedure, particularly with magnetic liquids, requires magnetic alternating field forces of approximately 15 to 20 kA/m at approximately 50 to 100 kHz. With a magnetic field exposure volume of 8 to 30 L, an effective energy capacity of approximately 18 kW to 80 kW must be produced. Since only a few watt are produced by the magnetic fluid in a patient""s body, the energy must be produced at a high-frequency to be able to transmit the necessary heat to effectively treat tumor tissue.
With the arrangement disclosed above it is possible to keep the exposure volume of the magnetic field, as well as any field leakage, advantageously low to limit the exposure to a targeted area in the patient""s body that is to undergo therapy. As a result, the required energy expenditure necessary for heat transmission, and ultimately heating tumor tissue, can be reduced. The shape of the magnetic yoke and pole shoes, together with their composition of ferrite segments, contribute to this efficiency by preventing undesirable excesses in flow density and magnetic field losses.
The utilization of ferrite segments in combination with high alternating frequency of approximately 50 to 100 kHz, makes possible an advantageous limitation of the magnetic field exposure volume, whereby only about 1/2000 of the energy, which would have an equivalent air volume, is moved in the ferrite volume. However, ferrite segments are prone to losses, whereby a doubling of the flow density in the work area can result in 5 to 6 times greater field losses. For this reason, appropriate measures are indicated below in order to keep the flow density low, and in particular, to avoid undesirable flow density increases, or at the very least reduce them considerably.
Ferrites are ceramic-like building blocks that can be produced in any desired form at a reasonable cost, and not necessarily in the overall form of the magnetic yoke used here. When combined into segments, these ferrite blocks allow an even energy flow through transitions between other segments and helps avoid flow density changes.
The magnetic field applicator, according to the invention, is equally well suited to carry out hyperthermia treatments and thermo-ablation procedures. In addition, the magnetic field applicator is suitable to warm other substances for medical applications other than in cancer therapy. Among these alternatives are all the heat-related medical applications such as heat-induced implant or stent regeneration, implant or stent surface activation, heating of inflamed body areas not affected by cancer for therapeutic purposes, facilitating contrast media distribution or improvement through magnetic alternating field excitation of super-paramagnetic contrast media, the mobilization of molecular-biological, cell-biological and development-physiological processes through excitation of magnet-carrier-assisted gene transfer systems, ligands, receptors, transmitters, other signal molecules as well as the triggering of material metabolism processes and endocrinal processes.
In the preferred embodiment, a component consisting of a lower transverse yoke element and associated pole shoe with magnetic disk-shaped coil are attached to a fixed position. A patient carriage with a patient support and carriage position display made of a plastic material can also be attached to the fixed pole shoe, whereby the patient need not be moved during the adjustment of the width of the space defining the exposure volume. Relative to this fixed position, a portal consisting of the two vertical yoke elements and the upper transverse yoke element with associated pole shoe and magnetic coil can then be shifted relative to this fixed component by means of a vertical displacement device for the adjustment of the width of the space defining the exposure volume.
A vertical displacement device can be made of a simple linear drive attached, preferably, to a vertical magnetic yoke element. For example, a self-inhibiting spindle drive can be used, so that the overall arrangement can be implemented very reliably and without danger that heavy magnetic yoke components may endanger a patient due to errors in the displacement device.
In a further advantageous development, the magnetic yoke can be held together in a supporting structure through which cooling air may be passed into the applicator and circulated through the cooling-air gap of the ferrite components for heat removal.
Depending on conditions and on special requirements, the space defining the exposure volume, and thereby the volume exposed to a magnetic field, can be limited laterally by field limiting coils and/or by bulkhead walls.
Accordingly, the magnetic field applicator can thus be used for a precisely localized non-contact hyperthermia on all kinds of tissues, bodies and objects incorporating magnetic substances. A preferred application of the magnetic field applicators is in the area of medicine, in particular in cancer therapy, whereby a magnetizable liquid with magnetizable nano-particles is preferably used as the magnetic substance to heat tissue when exposed to the magnetic field. A tumor area is to be heated locally by this method to temperature values above 41xc2x0 C.
Magnetic alternating fields with magnetic field forces of approximately 10 to 15 kA/m and frequencies from approximately 50 to 100 kHz are used for this purpose. In combination with the magnetic field applicator claimed above, the temperatures required for tumor therapy can then be reached for effective treatment. According to the invention, 1 to 2 kA/m is sufficient in a thermoseed application of the magnetic field applicator. Depending on the given situations, frequencies in a wider range, from 20 to 500 khz, may also be suitable.
In arrangements with cylinder-shaped coils surrounding the pole shoes, inductive heating causes temperatures to rises in the coils last winding that extends to the air space between the pole shoes, requiring extra measures for heat removal. The disk-shaped coil design with at least one winding extending helicoidally and forming an intermediate air gap between the coil and pole shoe, on the other hand, results in considerably lower flow densities on the surrounding edge of the assigned pole shoes, which reduces undesirable increases in flow density and heat buildup.
In one preferred embodiment of the invention, the magnetic disk-shaped coils made of spun copper-strand wire, should have one or more windings that extend helicoidally in order to minimize eddy current energy losses as much as possible.
In an especially advantageous embodiment, the pole shoes are made in a cylindrically shape and aligned facing parallel to each other, with the pole shoe ends opposing each other over a distance that defines the exposure volume. Accordingly, the magnetic disk-shaped coils are made in the form of rings surrounding the pole shoe ends and forming an intermediate air gap. This evens out the magnetic flow and is accompanied by a reduction of excess heating that would otherwise be increased at spatial corners and edges of the pole shoes.
Especially favorable conditions with respect to energy and flow are derived from the magnetic disk-shaped coil being placed as close as possible to the air space defining the exposure volume, particularly in a flush-surface arrangement with the assigned end of the pole shoe surface. Additional optimization is achieved if the intermediate air gap measures approximately {fraction (1/10)} of the diameter of the pole shoe (0.07 to 0.1 times) and the surrounding edge of the corresponding pole shoe surface is rounded off. In this manner damaging flow density excesses are reduced considerably.
The pole shoe diameter should be greater than the width of the space defining the exposure volume. This results in a reduction of any field leakage outside the pole shoes or the exposure volume of the magnetic field, so that the flow density throughout the ferrite segments, and therefore the losses in the ferrite material, can be kept at a relatively low level. If pole shoes with relatively small cross sections are used, the losses in the ferrite segments would be disproportionally high, making effective treatment of a tissue area difficult.
The magnetic yoke is composed of ferrite segments that have had any outer sintering layers produced during manufacturing removed, and the magnetically conductive surfaces ground flat to created uniform transitions throughout the yoke segments. The round pole shoes are accordingly composed of wedge-shaped ferrite segments like pieces of a cake, with adjoining surfaces also ground flat and freed of sintering layers.
In order to lower eddy current losses, the ferrite segments should be composed of ferrite plates aligned into adjacent rows, each row being separated from the other by plastic spacers defining an insulation/cooling gap. In the assembled state, these ferrite plates are aligned along the magnetic flow direction. To produce one-piece ferrite segments from ferrite plates, the plates are bonded to together via the spacers with adhesive. These ferrite segments are then assembled together to form the magnetic yoke. Also, narrow transition gaps are defined between the ferrite segments creating transitions, which help control the magnetic flow through the yoke and promote efficient heat removal.
Similarly, the wedge-shaped ferrite segments are combined to form the pole shoes, whereby a tubular central bore is left open that allows cooling air to be introduced for heat removal. A temperature-resistant two-component adhesive is preferably used to bond the ferrite plates.
The gaps between the ferrite plates serve as an electrical insulator and cooling channel, when cooling air is passed through the gaps. Cooling is necessary, despite ferrite""s low conductivity, since eddy currents are produced that trap in excess heat, which must be removed. Although liquid cooling would be more efficient, this cannot effectively be done in this case. Oil cooling is dangerous because of the flammability of oil, and equivalent non-flammable liquids generally contain toxins. Generally speaking, the density problems, especially with a movable yoke element, in combination with the other technical difficulties, could only be solved by a liquid coolant at high cost.
As indicated above, to have accurate control over the magnetic flow through transitions between ferrite segments, the magnetically inactive sintering layers of approximately 0.1 to 0.2 mm produced in the manufacturing process must be removed, and the magnetically conductive surfaces ground flat. Due to the high permeability of ferrite, the more even the surface, the better flow control there is between transitions of the magnetic yoke. It is especially advantageous to have forced-air gaps of approximately 2 to 3 mm between the transitions of the transversely movable yoke elements and adjoining vertical yoke elements, and at transitions between transverse yoke elements and the pole shoes, to help control the magnetic energy flow. In order to reduce the manufacturing costs and depending on conditions, a sintering layer may be left in a ferrite segment when placed in the vicinity of a relatively wide forced-air gap.